Use of real-world evidence to benchmark clinical trial results: A case study in von Hippel-Lindau (VHL) disease.

作者：W. Marston Linehan, Cathy Anne Pinto, Yanfang Liu, Claire Fox, Ananya Roy, Mengying Li, Rafia Bosan, Mark W. Ball, Kristin Choo, Rabindra Gautam, Deborah Nielsen, Beth Ryan, Alexis Rompré‐Brodeur, Cathy D. Vocke, Rodolfo F. Perini, Ramaprasad Srinivasan · 发表于：Journal of Clinical Oncology · 年份：2023 · DOI：10.1200/jco.2023.41.16_suppl.4531 · 研究领域：Cancer, Hypoxia, and Metabolism、Cancer Genomics and Diagnostics、Radiomics and Machine Learning in Medical Imaging

4531 Background: Data from a natural history study can be used to benchmark results from single arm trials with comparable ascertainment of exposures and outcomes. Despite limitations of externally controlled trials, natural history study data can provide important information, especially when clinical trial results provide compelling evidence of change in the established progression of disease. Such results could include partial or complete response for patients receiving drug in a disease where spontaneous regression is not observed. The aim was to conduct a natural history study to benchmark results of a Phase 2 single-arm trial (LITESPARK [LS]-004) for a new HIF-2a inhibitor (belzutifan) using comparable RECIST-based study endpoints. After a median follow-up of 37.8 months, the objective response rate (ORR) for patients with renal cell carcinoma (RCC) in LS-004 was 64.0% (95% CI: 50.6 to 75.8). Methods: A study of existing electronic medical records was conducted for VHL patients with disease-associated RCC undergoing active surveillance at the US National Cancer Institute. VHL patients with ≥1 cm solid RCC, confirmed by independent review, were followed until death or last encounter. Additional LS-004 exclusion criteria were applied to define the natural history study cohort: ≥3.0 cm tumor and procedure performed within 60 days, prior systemic oncologic therapy, and metastasis prior the index date. The index date was the date of the earliest radiology report with measura...